Unlocking the Health Benefits of Tauroursodeoxycholic Acid (TUDCA)
Tauroursodeoxycholic acid, more commonly known as TUDCA for short, is a naturally occurring bile acid found in the human body that has been gaining a lot of attention from practitioners as well as popularity in the health & wellness industry for its health benefits. TUDCA has amassed a significant number of animal & human studies as well as a number of clinical trials currently under way demonstrating it’s potential to aid in the prevention and treatment of numerous health conditions. In this blog, we will discuss the health benefits of TUDCA, what it is, how it works, and whether it is safe to supplement.
What is Tauroursodeoxycholic Acid (TUDCA)?
Tauroursodeoxycholic acid, or TUDCA, is a naturally occurring bile acid found in the body. It is a derivative of the primary bile acid, ursodeoxycholic acid (UDCA), which is produced in the liver and stored in the gallbladder.
TUDCA is a powerful antioxidant and has been studied extensively for its potential health benefits. It has been shown to reduce inflammation, improve liver function, and protect against neurological diseases. It has been shown to have protective effects on the eyes, gastrointestinal tract including promoting a healthy gut microbiome. Historically TUDCA has been used to treat cholestatic liver diseases and gallstones.
TUDCA is available as a supplement and is becoming more widely available in Australia.
What are Bile Acids?
Bile acids are steroid molecules produced in the liver from cholesterol & stored in the gallbladder. From there they are released into the small intestine where they help to break down and absorb fats and oils. They emulsify fat droplets so that they can be absorbed by the intestines, and as such Bile acids are also responsible for aiding in the digestion of fat-soluble vitamins, such as vitamins A, D, E, and K. Cholesterol excretion is another important feature of bile acids and having an anti-microbial effect in the gut covers the main three roles of bile acids in the human body.
There are two types of bile acids
1) Primary bile acids which are produced in the liver and
2) Secondary bile acids are made via gut bacteria
For the purpose of this write up I'll focus two of the many different bile acids, TUDCA and UDCA. What makes UDCA & TUDCA unique in comparison to other bile acids is that they have a higher affinity to water (more hydrophilic), and thus you will sometimes see TUDCA referred to as a water-soluble bile acid.
How TUDCA works
As I've touched on already, TUDCA being a bile acid is responsible for aiding in the digestion of fats and oils. However the mechanisms and benefitis of TUDCA extend well beyond simply the gut & digestion. TUDCA has been shown to reduce inflammation and oxidative stress. It is believed to do this by inhibiting the release of inflammatory cytokines, which are proteins that play a role in the body's inflammatory response. By reducing inflammation, TUDCA can help to protect against several diseases, including cardiovascular disease, diabetes, neurodegenerative diseases and obesity. TUDCA acts as a chemical chaperone to maintain the stability and correct folding of proteins. Regulates and inhibits the apoptotic cascade, in otherwords buts the brakes on premature cell death.
UDCA and TUDCA can cross the blood–brain barrier (BBB) and therefore potentially exert neuroprotective benefits on the brain which has shown promise in some early studies on animals and humans with Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Huntington's disease and Parkinson's disease.
Benefits of TUDCA
TUDCA has several potential health benefits, including the following:
Improved eye health
Improved brain health can potentially beneficial for neurodegenerative disorders
Significantly reduces brain injury associated with Intracerebral haemorrhage (in rat studies)
Supports a healthy gut microbiome
Reduces liver enzymes & protect against liver damage
Improves Insulin resistance
Promotes healthy blood vessel formation
TUDCA and Eye Health
TUDCA has been studied extensively for its potential to treat and prevent eye conditions such as Retinitis pigmentosa, and age-related macular degeneration. Other studies have found TUDCA supplementation to have protective effects in diabetic retinopathy in rats. It is also believed to reduce oxidative stress in the eyes as well as acting as an anti-inflammatory which can help to protect against age-related vision loss. TUDCA has been shown to have potent anti-apoptotic effects on the photoreceptors of the eye. A recent study investigating the hypothesis of TUDCA preserving visual and retinal function in diabetic retinopathy using the mouse model, confirmed that TUDCA was able to preserve visual function.
TUDCA and Brain Health
Studies have shown that TUDCA can help protect against oxidative stress & reduce inflammation in the brain, thus serving as a mediator in preventing premature apoptosis of brain cells. This is one of the main mechanisms why researchers believe TUDCA has been shown to slow the progression of neurodegenerative disorders. Another mechanism that is proposed is that TUDCA acts as a chemical chaperone to maintain the stability and correct folding of proteins. TUDCA has also been shown to regulate certain genes involved with cell cycle regulation and apoptosis pathways which favours cell survival.
Image below shows the proposed physiological mechanisms of TUDCA .
TUDCA proposed mechanisms (Khalaf et al., 2022)
TUDCA has been studied as a potential treatment for neurological diseases such as Amyotrophic Lateral Sclerosis, Alzheimer's disease, Huntington's disease and Parkinson's disease. One of the key hallmark features that are consistent with these neurodegenerative disorders is where the process of normal programmed cell death (apoptosis) becomes compromised & essentially leads to premature cell death. It's important to note that the process of apoptosis once begun can not stop itself. Two key processes that have been linked to the dysregulation of apoptosis include;
i) stress to the endoplasmic reticulum such as in the case of excessive amounts of reactive oxygen species (ROS) and
ii) an accumulation of misfolded or mutated proteins, such as a buildup of alpha-synuclein in the brain with Parkinson's Disease which leads to a depletion of the dopamine-producing cells.
A pilot study in human's investigated whether a TUDCA supplement could have any benefit in patients with ALS. Patients who were given 2 grams of TUDCA per day were associated with a slower deterioration of ALS symptoms compared to the placebo group. The researchers concluded
This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.
Of the neurodegenerative disorders, ALS to date is the only one that has had a human clinical trial looking at TUDCA and its beneficial effects, the others are all done either in vitro or in animal models which have shown promising signs and provided substantial evidence for the therapeutic properties of TUDCA in halting apoptotic pathways. We will certainly see more human clinical studies coming out in the very near future.
Image from (Zangerolamo et al., 2021) - Summary of TUDCA benefits with Neurodegenerative diseases
TUDCA & Multiple Sclerosis
In a recent study researchers investigated firstly, whether bile acid metabolites were different in individuals with Multiple Sclerosis (MS) to individuals without MS and secondly, whether supplementation with TUDCA affected glial and immune cells in MS brain tissue. Lower levels of circulating bile acids were noted in MS individuals as well as 2 key bile acid receptors were found to be present on glial and immune cells in MS brain tissue. The researchers found that TUDCA supplementation acted as a strong anti-inflammatory agent on specific nerve cells which are associated with MS pathology. Next up they observed in the mouse model of MS, supplementing with TUDCA via its actions on one of these bile acid receptors was able to ameliorate the disease.
TUDCA Supports a Healthy Gut Microbiome & Promotes Gut Health
TUDCA has been studied for its potential to support a healthy gut microbiome. Studies have shown that TUDCA can help to reduce inflammation and oxidative stress in the gut, which in turn can help to improve digestion and absorption of essential nutrients.
TUDCA has shown convincing mechanistic benefits to the gut epithelial cells. Intestinal inflammation has been linked to endoplasmic reticulum (ER) stress mechanisms & TUDCA has been shown to have a potent positive effect at decreasing ER stress. Given these findings TUDCA has been suggested by researchers to be considered as a therapy for inflammatory bowel diseases (IBD)
We conclude that TUDCA and UDCA are potent anti-aggregants for the resolution of ER stress in intestinal epithelial cells and should be considered as a potential drug target to resolve ER stress mechanisms underlying the pathology of IBD.
TUDCA has been shown to potentially play a role in treating gastritis associated with bile acid reflux via it's stomach lining protective mechanisms.
TUDCA has proven to be of critical importance in the treatment of Neonatal necrotizing enterocolitis (NEC) in mice studies. NEC is characterised by severe gut inflammation and intestinal cell apoptosis in which case can be life-threatening. In a fairly recent study investigating TUDCA in the treatment of NEC the authors concluded:
Our results showed that TUDCA reduced mortality rates, prolonged survival times, significantly diminished intestinal damage, and inhibited intestinal inflammation in the mouse model of NEC.
TUDCA & Insulin Resistance
Insulin Resistance is a significant health burden in the modern western world as it is involved in the pathogenesis of the key metabolic disorders associated with obesity. TUDCA has been shown to have a positive effect on insulin resistance and blood glucose in human studies. One particular study looked at 4 weeks of supplementation with TUDCA & its effect on insulin resistance in obese males & females. In obese, insulin-resistant subjects supplementation with TUDCA increased liver & muscle insulin sensitivity by 30%. The researches noted the effects of TUDCA on insulin sensitivity seemed to be comparable to that of some medications as notied in the following comment:
Moreover, the magnitude of the improvement in hepatic and muscle insulin sensitivity (both ∼30%) is similar to the insulin-sensitizing effects of currently available diabetes medications, such as thiazolinediones and metformin
A study looking at TUDCA supplementation and it's effects on chemically induced high blood pressure & obesity-induced caridac contractile dysfunction in mice found that 5 weeks of TUDCA supplementation lowered systolic blood pressure and improved glucose intolerance.
TUDCA Reduces Liver Enzymes
TUDCA is believed to help reduce inflammation and oxidative stress in the liver bile duct system, which can help to protect against damage and disease. Studies have shown that TUDCA can help to reduce levels of liver enzymes, which can help to protect against liver damage, reduce the risk of liver disease & promote overall liver health. One particular study compared 6 months supplementation of TUDCA (750mg per day) or UDCA and their impact on liver function tests in patients with liver cirrhosis. Subjects in the TUDCA group had greater improvements in their liver function tests than those in the UDCA group. Another study that was for only 2 months supplementation of 750mg TUDCA per day in individuals with primary biliary cirrhosis found that in all patients their liver enzyme markers were significantly improved. Of note there were no reported adverse reactions with the participants.
TUDCA vs NAC, TUDCA vs Milk Thistle
TUDCA is often compared to other supplements such as N-acetylcysteine (NAC) and milk thistle, as they all have potential health benefits especially with regard to liver & gallbladder health. However, TUDCA is believed to be more effective than NAC and milk thistle for reducing inflammation and oxidative stress, as well as for supporting a healthy gut microbiome. It is also thought to be more effective for reducing levels of liver enzymes. Ultimately they all have different mechanisms & likely to work in a complimentary fashion. One research paper did indeed show that TUDCA & NAC combined together was indeed more effective at treating Acetaminophen or paracetamol overdose in mice than in isolation. This is a significant finding as the only current pharmacological therapy for Acetaminophen or paracetamol overdose is NAC. One important point to mention however is the fact that TUDCA has a very good track record for minimal side effects.
Where To Buy TUDCA In Australia
At this point you may be wondering what is the best TUDCA Supplement & where to buy tudca in australia....
TUDCA is available as a supplement and is widely available in Australia. It is important to note that not all TUDCA supplements are created equal, and it is important to do your research and look at all the ingredients before you buy. I have been using BodyBio TUDCA in clinical practice since it first came available and they are highly regarded in the supplement industry as leading producers of the highest quality and standard TUDCA supplements. There is no way to achieve the powerful benefits of Tudca without strict internal and external quality control. The raw materials of BodyBio Tudca undergo extensive testing for the presence of mold before encapsulation. BodyBio Tudca supplement is free of wheat, gluten, yeast, soy, dairy, artificial colours, and resins. You can find BodyBio TUDCA at our online store. https://www.holisticlifestyler.com/new-products.
FAQ
What’s the difference between TUDCA and UDCA?
UDCA is a secondary bile acid produced exclusively by intestinal bacteria. UDCA is then directed to the liver and is conjugated with taurine to form TUDCA, in essence TUDCA is the “taurine conjugated” form of UDCA
Studies comparing UDCA & TUDCA for therapeutic efficacy tends to favour TUDCA due to it being more hydrophilic, better absorbed & reduced biotransformation to more hydrophobic metabolites.
Are there any side effects of TUDCA Supplements & is TUDCA Safe?
TUDCA is generally considered to be safe and well-tolerated when taken in the recommended amounts. Some have experienced diarrhea when taking more than 1500 mg daily, which is not recommended. There are no other reported TUDCA side effects. The research studies have consistently noted an incredibly low rate of side effects other than the occasional mild case of diarrhea.
Where does TUDCA come from?
Bear bile has been used in Traditional Chinese Medicine for thousands of years due to its therapeutic potential and clinical applications. Thankfully in more recent times TUDCA supplements are made from non animal derived synthetic options.
When to take TUDCA?
There are no hard and fast rules, however when taken with meals especially high fat meals TUDCA will help with digestion. Some people have reported taking TUDCA when fasting with no adverse effects.
References
Berger, E. and Haller, D. (2011) “Structure–function analysis of the tertiary bile acid TUDCA for the resolution of endoplasmic reticulum stress in intestinal epithelial cells,” Biochemical and Biophysical Research Communications, 409(4), pp. 610–615. Available at: https://doi.org/10.1016/j.bbrc.2011.05.043.
Ceylan-Isik, A.F., Sreejayan, N. and Ren, J. (2011) “Endoplasmic reticulum chaperon tauroursodeoxycholic acid alleviates obesity-induced myocardial contractile dysfunction,” Journal of Molecular and Cellular Cardiology, 50(1), pp. 107–116. Available at: https://doi.org/10.1016/j.yjmcc.2010.10.023.
Cho, J.G. et al. (2015) “Tauroursodeoxycholic acid, a bile acid, promotes blood vessel repair by recruiting vasculogenic progenitor cells,” Stem Cells, 33(3), pp. 792–805. Available at: https://doi.org/10.1002/stem.1901.
Elia, A.E. et al. (2015) “Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis,” European Journal of Neurology, 23(1), pp. 45–52. Available at: https://doi.org/10.1111/ene.12664.
Invernizzi, P. et al. (1999) “Differences in the metabolism and disposition of Ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis,” Hepatology, 29(2), pp. 320–327. Available at: https://doi.org/10.1002/hep.510290220.
Kars, M. et al. (2010) “Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women,” Diabetes, 59(8), pp. 1899–1905. Available at: https://doi.org/10.2337/db10-0308.
Khalaf, K. et al. (2022) “Tauroursodeoxycholic acid: A potential therapeutic tool in neurodegenerative diseases,” Translational Neurodegeneration, 11(1). Available at: https://doi.org/10.1186/s40035-022-00307-z.
Li, P. et al. (2019) “TUDCA attenuates intestinal injury and inhibits endoplasmic reticulum stress-mediated intestinal cell apoptosis in necrotizing enterocolitis,” International Immunopharmacology, 74, p. 105665. Available at: https://doi.org/10.1016/j.intimp.2019.05.050.
Mertens, K.L. et al. (2017) “Bile acid signaling pathways from the enterohepatic circulation to the Central Nervous System,” Frontiers in Neuroscience, 11. Available at: https://doi.org/10.3389/fnins.2017.00617.
Pan, X.-li et al. (2013) “Efficacy and safety of Tauroursodeoxycholic acid in the treatment of liver cirrhosis: A double-blind randomized controlled trial,” Journal of Huazhong University of Science and Technology [Medical Sciences], 33(2), pp. 189–194. Available at: https://doi.org/10.1007/s11596-013-1095-x.
Parry, G.J. et al. (2010) “Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic acid in patients with amyotrophic lateral sclerosis,” Clinical Neuropharmacology, 33(1), pp. 17–21. Available at: https://doi.org/10.1097/wnf.0b013e3181c47569.
Piepoli, A.L. et al. (2002) “Tauroursodeoxycholic acid reduces damaging effects of taurodeoxycholic acid on fundus gastric mucosa,” Archives of Physiology and Biochemistry, 110(3), pp. 197–202. Available at: https://doi.org/10.1076/apab.110.3.197.8295.
Rodrigues, C.M. et al. (2003) “Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats,” Proceedings of the National Academy of Sciences, 100(10), pp. 6087–6092. Available at: https://doi.org/10.1073/pnas.1031632100.
Zangerolamo, L. et al. (2021) “The bile acid TUDCA and neurodegenerative disorders: An overview,” Life Sciences, 272, p. 119252. Available at: https://doi.org/10.1016/j.lfs.2021.119252.